SUMMARY ? PROJECT 5 Conte Center Project 5 investigates the stress-diathesis model of suicidal behavior. Specifically, we examined stress response using the Trier Social Stress Test (TSST) and Ecological Momentary Assessment of daily stressors (EMA), and studied the role of childhood adversity (CA) and impulsive aggression in depressed suicide attempters, depressed nonattempters and healthy volunteers. We found that while aggression was higher in attempters, stress responsivity was heightened only in attempters with high reactive/impulsive aggression. We also observed that this highly stress responsive, impulsive group displayed a cluster of characteristics: a pattern of frequent brief, highly variable suicidal ideation (SI) that correlated to a history of CA and increased in response to daily stressors, together with poorer emotion regulation. In contrast, we found that high planning of suicide attempts was related to family history of suicide and persistent SI. Thus, we observe different sets of characteristics associated with suicidal outcomes at opposite ends of a continuum from very impulsive to highly planned and deliberate suicidal behaviors. In this application, we expand our work by further exploring the neurobiological and cognitive underpinnings of impulsivity/planning of suicide attempts. Specifically, we will examine executive functioning and emotion regulation strategies (in vivo during the TSST and EMA) and determine their relationships with suicidal behavior, SI variability and stress response. A second promising extension of our work is to study related stress response mechanisms, particularly inflammation, which is associated with suicide risk factors of CA and aggression. We have shown that the cytokine-activated kynurenine pathway is upregulated in attempters, and that lower levels of the anti-inflammatory polyunsaturated fatty acid (PUFA) docosahexaenoic acid predict suicide attempts, and we have pilot data on elevated IL-6 in high risk attempters, consistent with previous literature. A clearer delineation of the behavioral and physiological pathways to suicidal behavior will improve prevention by identifying a more personalized approach depending on the risk profile.